Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the AtheroGene study

BACKGROUND: Tissue factor (TF) and its specific inhibitor, tissue factor pathway inhibitor (TFPI), are important contributors to the initiation of the coagulation process. OBJECTIVES: To compare plasma levels of soluble TF (sTF) and free-TFPI (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) and to assess the impact of the two variables on long-term prognosis. PATIENTS/METHODS: Patients with SAPs (n = 1146) and acute coronary syndrome (n = 523) from the AtheroGene study were included and followed for 2.3 years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI levels, but not on sTF levels, patients having received UFH before blood drawing were excluded from the analyses on f-TFPI (n = 226). RESULTS: On admission, no significant differences in sTF levels were observed between SAP and ACS patients. By comparison to patients with stable angina, f-TFPI levels significantly increased in patients with acute unstable angina and further increased in patients presenting with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (P < 10(-4)). Among the 1669 individuals with a coronary artery disease, 56 died from a cardiovascular cause. In prospective analyses, high sTF levels were independently associated with an increased risk of cardiovascular death in individuals with ACS (fully adjusted hazard ratio associated with one quartile increase = 2.06; 95% confidence interval 1.24-3.45; P = 0.006) but not in those with SAP (hazard ratio = 1.07; 95% confidence interval 0.78-1.46; P = 0.67). In SAP and ACS patients, high f-TFPI levels were not independently associated with an increased risk of cardiovascular death. CONCLUSIONS: Plasma sTF levels were predictive of cardiovascular mortality in individuals with ACS, whereas f-TFPI levels were associated with the severity of myocardial damage on admission but were not independently related to outcome.     

Thrombin generation during reperfusion after coronary artery bypass surgery associates with postoperative myocardial damage

BACKGROUND: Cardiopulmonary bypass and coronary artery bypass grafting (CABG) result in significant thrombin generation and activation of fibrinolysis. Thrombin contributes to myocardial ischemia-reperfusion injury in animal studies, but the role of thrombin in myocardial damage after CABG is unknown. OBJECTIVES: We measured thrombin generation and fibrin turnover during reperfusion after CABG to evaluate their associations with postoperative hemodynamic changes and myocardial damage. METHODS: One hundred patients undergoing primary, elective, on-pump CABG were prospectively enrolled. Plasma prothrombin fragment F(1+2) and D-dimer were measured preoperatively and at seven time points thereafter. Mass of the Mb fraction of creatine kinase (Ck-Mbm) and troponin T (TnT) were measured on the first postoperative day. RESULTS: Reperfusion induced an escalation of thrombin generation and fibrin turnover despite full heparinization. F(1+2) during early reperfusion associated with postoperative pulmonary vascular resistance index. F(1+2) at 6 h after protamine administration correlated with Ck-Mbm (r = 0.40, P < 0.001) and TnT (r = 0.44, P < 0.001) at 18 h postoperatively. Patients with evidence of myocardial damage (highest quintiles of plasma Ck-Mbm and TnT) had significantly higher F(1+2) during reperfusion than others (P < 0.002). Logistic regression models identified F(1+2) during reperfusion to independently associate with postoperative myocardial damage (odds ratios 2.5-4.4, 95% confidence intervals 1.04-15.7). CONCLUSIONS: Reperfusion caused a burst in thrombin generation and fibrin turnover despite generous heparinization. Thrombin generation during reperfusion after CABG associated with pulmonary vascular resistance and postoperative myocardial damage.     

Myeloperoxidase level in patients with stable coronary artery disease and acute coronary syndromes

Background No studies have measured plasma myeloperoxidase (MPO) across the entire spectrum of patients with coronary artery disease (CAD). The aim of the study was to compare MPO level across the entire spectrum of CAD, to assess the accuracy of MPO in predicting acute coronary syndromes and to define independent correlates of MPO level. Design This case–control study included 874 patients with angiographically proven CAD. Cases included 680 patients with CAD (382 patients with stable CAD, 107 patients with non-ST-segment elevation acute coronary syndromes and 191 patients with ST-segment elevation acute myocardial infarction). Controls included 194 subjects with normal coronary angiograms. MPO was measured using an enzyme immunoassay before angiography and heparin administration. Results MPO level [median (25th–75th percentiles)] was 74·5 (52·5–135·3) µg L⁻¹ in cases vs. 61·2 (44·6–80·9), µg L⁻¹ in controls (P < 0·001). MPO level was 61·2 (47·5–85·8), µg L⁻¹ in patients with stable CAD, 99·2 (62·2–154·9), µg L⁻¹ in patients with non-ST-segment elevation acute coronary syndromes and 129·5 (72·2–216·0) µg L⁻¹ in patients with acute myocardial infarction (P < 0·001). Elevated MPO level was associated with acute coronary syndromes with an area under receiver operating characteristic (ROC) curve of 0·731 (95% confidence interval 0·692–0·770; P < 0·001). Independent correlates of MPO level were acute coronary syndrome (P < 0·001), high-sensitivity C-reactive protein (P = 0·007), creatinine (P = 0·026), left ventricular ejection fraction (P = 0·027, negative association) and smoking (P = 0·028). Conclusions MPO level is elevated in patients with CAD and higher levels of MPO were found with progression of CAD from stable CAD to non-ST-segment elevation acute coronary syndromes and to acute myocardial infarction.     

The composition and daily variation of microparticles in whole blood in stable coronary artery disease

Introduction: The knowledge of circadian variation of microparticles (MPs) in stable coronary artery disease (SCAD) is limited. The aim of this study was to evaluate the daily variation of platelet-, endothelial- and monocyte-derived MPs in whole blood and their tissue factor expression (TF) in SCAD and whether these MPs were related to other endothelial and coagulation markers. Materials and methods: Serial blood samples from patients with SCAD were collected during one day. Flow cytometry was used to evaluate the amount of large MPs 0.5–1.0 μm, positive for annexin, and their expression of CD41, CD62P, CD144, CD14 and TF. The lag time and endogenous thrombin potential (ETP) was calculated by Calibrated Automated Thrombogram and soluble (s)P-selectin, sTF and vWF by ELISA. Results: The majority of MPs in whole blood consisted of CD41?+?MPs with no significant daily variation. In contrast, the concentration of CD62P?+?MPs described a daily variation with the lowest concentrations found in the evening (p?=?0.031). CD62P?+?and CD144?+?MPs had the highest expression of TF, 52.6% and 42.9%, respectively, and correlated to the endothelial activity evaluated by vWF. There was a circadian rhythm of lag time (p?p?=?0.001). The CD62P+, CD14?+?and CD144?+?MPs correlated to the lag time. Conclusion: The different subsets of platelet-, endothelial- and monocyte-derived MPs do not present the same circadian variation and they differ in TF expression in SCAD. The MPs from activated platelets, endothelial cells and monocytes exist in low concentrations in whole blood but are related to the endothelial and coagulation activity found in SCAD.     

Thrombin generation profiles in deep venous thrombosis

BACKGROUND: Reliable markers and methods to predict risk for thrombosis are essential to clinical management. OBJECTIVE: Using an integrated approach that defines an individual's comprehensive coagulation phenotype might prove valuable in identifying individuals at risk for experiencing a thrombotic event. METHODS: Using a numerical simulation model, we generated tissue factor (TF) initiated thrombin curves using coagulation factor levels from the Leiden Thrombophilia Study population and evaluated thrombotic risk, by sex, age, smoking, alcohol consumption, body mass index (BMI) and oral contraceptive (OC) use. We quantitated the initiation, propagation and termination phases of each individuals' comprehensive TF-initiated thrombin generation curve by the parameters: time to 10 nm of thrombin, maximum time, level and rate (MaxR) of thrombin generated and total thrombin. RESULTS: The greatest risk association was obtained using MaxR; with a 2.6-fold increased risk at MaxR exceeding the 90th percentile. The odds ratio (OR) for MaxR was 3.9 in men, 2.1 in women, and 2.9 in women on OCs. The association of risk with thrombin generation did not differ by age (OR:2.8 OR:2.5), BMI (OR:2.9 OR:2.3) or alcohol use. In both numerical simulations and empirical synthetic plasma, OC use created extreme shifts in thrombin generation in both control women and women with a prior thrombosis, with a larger shift in thrombin generation in control women. This suggests an interaction of OC use with underlying prothrombotic abnormalities. CONCLUSIONS: Thrombin generation based upon the individual's blood composition is associated with the risk for thrombosis and may be useful as a predictive marker for evaluating thrombosis on an individual basis.     

ADAMTS4 level in patients with stable coronary artery disease and acute coronary syndromes

Objective

A recent study indicates that ADAMTS4 (a disintegrin and metalloprotease with thrombospondin motifs 4) was expressed in macrophage rich areas of human atherosclerotic carotid plaques and coronary unstable plaques suggesting a pathogenic role in the development of acute coronary syndromes (ACS). The aim of the study was to compare ADAMTS4 across the entire spectrum of coronary artery disease (CAD) and to investigate the temporal profiles of ADAMTS4.

Methods

Plasma levels of ADAMTS4 were measured in patients with stable effort angina pectoris (SAP), ACS and in controls. Venous blood was sampled upon admission before angiography and drug administration. In patients with ACS who underwent medical treatment, serial blood samples were also collected on days 1, 2, 3, 5 and 7 after admission. ADAMTS4 was measured using an enzyme immunoassay.

Results

Plasma ADAMTS4 level in cases was significantly greater than in controls (P < 0.001). Higher levels of ADAMTS4 were found with progression of CAD from SAP to unstable angina pectoris (UAP) to non-ST-segment elevation acute myocardial infarction (NSTEMI) and to ST-segment elevation acute myocardial infarction (STEMI) (P < 0.001). Elevated ADAMTS4 level was associated with ACS with an area under receiver operating characteristic (ROC) curve of 0.753 (95% CI 0.654–0.851; P < 0.001). The pattern of ADAMTS4 release observed was clearly different in various forms of ACS. ADAMTS4 showed a weak correlation with high-sensitivity C-reactive protein (hs-CRP); however, no significant correlation was found between ADAMTS4 and troponin T (TnT) in ACS patients.

Conclusions

Serial changes in plasma ADAMTS4 were documented in patients with ACS and may serve as a marker of plaque destabilization.     

Thrombin generation in vascular tissue

BACKGROUND: Classically, it is thought that the vast majority of thrombin is generated on the surface of platelets, however, thrombotic events occur in patients despite treatment with potent antiplatelet agents. METHODS AND RESULTS: In freshly harvested left internal mammary artery (IMA) sections, addition of CaCl2 and platelet-poor plasma (PPP) were sufficient to stimulate a profound burst of thrombin and this effect was inhibited by antitissue factor antibodies. Ultracentrifugation of PPP to remove platelet microparticles had no effect on thrombin generation. Both the extrinsic and factor VIII-dependent pathways were necessary for IMA-supported thrombin generation as PPP derived from individuals deficient in factors V, VII, VIII or X did not support thrombin production. Small amounts of thrombin were generated utilizing factor IX (FIX)-deficient plasma, however, thrombin was not generated by aorta from FIX-deficient mice when FIX-deficient plasma was used. The addition of non-lipidated tissue factor (0.6 pM) and CaCl2 to actively proliferating cultured human aortic smooth muscle cells (SMC) resulted in a pronounced burst of thrombin generation occurring between 3 and 15 min after treatment. In the absence of tissue factor, thrombin was generated but at a slower rate and with a peak value 26% of that observed in the presence of tissue factor. CONCLUSION: Significant thrombin generation can occur on vascular tissue in the absence of platelets or platelet microparticles and on the surface of non-apoptotic SMC.     

Apolipoprotein C‐III predicts cardiovascular mortality in severe coronary artery disease and is associated with an enhanced plasma thrombin generation

Summary. Background: Apolipopoprotein C‐III (apo C‐III) plays a pivotal role in controlling plasma triglyceride (TG) and contributes to the atherogenic properties of TG‐rich lipoproteins. Objectives: (i) To examine the predictive value of serum apo C‐III for cardiovascular mortality in the setting of secondary prevention of coronary artery disease (CAD); and (ii) to evaluate possible associations between apolipoprotein levels and the thrombin generation assay, a global test to estimate plasma thrombogenic potential. Methods and results: A cohort of 633 patients with angiographically proven CAD was prospectively followed for a median follow‐up of 57 months. The large majority of them (92%) underwent coronary (endovascular or surgical) revascularization. During the follow‐up, 91 (14.3%) out of 633 patients died, with 64 events (10.1%) attributed to cardiovascular causes. After adjustment for all the other predictors of mortality during univariate analysis (i.e. age, statin therapy, myocardial infarction history, diabetes, hs‐CRP and creatinine), elevated apo C‐III levels (≥ 10.5 mg dL^?1– the median value) significantly predicted both total and cardiovascular mortality (HR for total mortality 2.22 with 95% CI 1.16–4.24; HR for cardiovascular mortality 2.35 with 95% CI 1.19–4.62). In a subgroup of 225 subjects, apo C‐III levels were significantly associated with endogenous thrombin potential in regression models (standardized β coefficient = 0.207, P = 0.002). Conclusions: Basal concentrations of apo C‐III levels ≥ 10.5 mg dL^?1 in CAD patients independently predicted cardiovascular mortality during the subsequent 5‐year period. Such concentrations were associated with an enhanced plasma endogenous thrombin generation, suggesting a complex interplay between TG‐rich particles and the coagulation cascade as well as a new ‘thrombogenetic’ role for apo C‐III.     

冠心病患者心血管意外和凝血功能的相关性研究

目的深入研究冠心病患者凝血功能与心血管意外的关系,我们对患者血液中的von willebrand因子(vWF)、抗凝血酶原复合物(TAT),D-二聚体(D-dimers),抗纤维蛋白溶酶复合物(PAP)和心血管意外死亡发生率的关系进行了研究。方法 1057名经冠状造影证实有冠状血管粥样硬化的患者,平均随访时间为6.6年,在此期间有135名患者死亡心血管意外,97名患者发生非致死性心血管意外。高浓度的凝血状态和心血管意外死亡有关,但与非死亡性心血管意外无关。在去除与心血管意外发生的传统因素(C反应蛋白)外,vWF,纤维蛋白原,TAT,D-二聚体,PAP与心血管意外发生的相关性P值分别为0.20,0.011,0.026,0.019,和0.01。在多因素COX模型中,D-dimers和纤维蛋白原是独立影响因素,危害比(95%CI)分别为1.27(1.04-1.55)和1.29(1.09-1.53)。结果结论在冠状血管疾病患者中,纤维蛋白原和D-dimer可以作为预测冠心病患者心血管死亡的独立因素,对此类患者有必要进行预防性的抗凝治疗。     

青年冠心病患者危险因素分析

目的　探讨 5 0岁以下冠心病患者危险因素 ,对高危青年人的冠心病一级预防提供参考。方法　根据 15 6例冠状动脉造影结果将 5 0岁以下行冠脉造影者分为冠心病组 (89例 )和非冠心病组 (6 7例 ) ,收集临床心血管危险因素资料进行Logistic多因素回归分析。结果　 15 6例冠状动脉造影者中 89例诊断为冠心病 (5 7.1% ) ,6 7例无冠心病(42 .9% )。Logistic多因素回归分析显示冠心病家族史、血浆总胆固醇水平及吸烟为冠心病的独立危险因素 ,其相关系数分别为 0 .6 3、0 .5 0、0 .97,优势比 (OR)分别为 1.0 6、1.6 5、2 .6 4 (P <0 .0 5 )。结论　冠心病家族史、高血浆总胆固醇水平及吸烟是青年人冠心病的发生的高危因素 ,对这类人群应尽早干预。     

Delays in presentation with acute coronary syndrome in people with coronary artery disease in Australia and New Zealand

Objectives: To report time from the onset of symptoms to hospital presentation in Australian and New Zealand patients with subsequently confirmed acute coronary syndrome, and to identify factors associated with prehospital delay time in these patients. Methods: Patients with coronary artery disease enrolled in a randomized clinical trial testing an intervention to reduce delay in responding to acute coronary syndrome symptoms had been followed for 24 months. In cases of admission to the ED for possible acute coronary syndrome, medical records were reviewed to determine the diagnosis, prehospital delay time, mode of transport to the hospital and aspirin use before admission. Clinical and demographic data were taken from the trial database. Results: Patients (n= 140) had an average (SD) age of 67.3 (11.5) years; 36% were female. Two‐thirds of patients went to hospital by ambulance and 89.3% had a final diagnosis of unstable angina. The median time from onset of symptoms to arrival at the ED was 2 h and 25 min (interquartile range 1:25–4:59); 12.1% arrived ≤ 1 h and 66% within 4 h. Multiple linear regression analysis showed that use of ambulance (Beta = 0.247, P= 0.012) and younger age (Beta = 0.198, P= 0.043) were independent predictors of shorter delay times. Conclusion: The time from the onset of symptoms to hospital presentation was too long for maximal benefit from treatment in most patients. Further efforts are needed to reduce treatment‐seeking delay in response to symptoms of acute coronary syndrome.     

预防急性冠脉综合征的治疗及护理进展

急性冠脉综合征(ACS)是以冠状动脉粥样硬化斑块破裂或侵蚀继发的完全或不完全闭塞性血栓形成为病理基础的一组临床综合征。预防动脉粥样硬化斑块破裂是预防急性冠脉综合征的最主要手段。目前新的研究思路是确定早期处理“ACS的规则”。本文阐述了预防急性冠脉综合征的治疗进展及护理对策。     

血清补体C1q水平预测与区分急性冠脉综合征和稳定性冠心病的临床价值

目的探讨冠心病(CAD)患者血清补体1q(C1q)的水平,评估其对急性冠脉综合征(ACS)和稳定性冠心病(SCAD)的预测与区分价值。方法选取52例ACS患者、66例SCAD患者和54例健康人对照者纳入研究。采用免疫透射比浊法测定血清C1q、ELISA法测定血清氧化低密度脂蛋白(ox-LDL);同时分析血清总胆固醇、三酰甘油(TG)、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平;计算CAD患者Gensini积分;并通过逐步多元线性回归分析和Logistic回归分析探讨C1q对ACS和SCAD的预测与区分价值。结果与健康人对照组相比,ACS(C1q:t=4.405,P0.001;ox-LDL:Z=5.941,P0.001)和SCAD(C1q:t=2.320,P=0.022;ox-LDL:Z=4.119,P0.001)组血清C1q、ox-LDL水平均显著升高;且ACS组血清C1q(t=2.344,P=0.021)、ox-LDL(Z=2.166,P=0.030)水平显著高于SCAD组。ACS组血清C1q水平与ox-LDL(r=0.246,P=0.028)、TG(r=0.232,P=0.002)及Gensini积分(r=0.341,P=0.020)呈显著正相关;逐步多元线性回归分析显示,在校正了年龄、性别及其他生化指标的影响后,ACS患者血清ox-LDL水平仍与C1q呈显著独立相关(β=0.676,P=0.045,校正R2=0.380)。多元Logistic回归分析显示,血清C1q、ox-LDL水平的升高均与ACS(C1q:OR=1.05,95%CI=1.03~1.08,P0.001;ox-LDL:OR=1.18,95%CI=1.08~1.29,P0.001)、SCAD(C1q:OR=1.04,95%CI=1.01~1.06,P=0.003;ox-LDL:OR=1.11,95%CI=1.03~1.18,P=0.004)的发生密切相关;且有助于区分ACS和SCAD发生(C1q:OR=1.01,95%CI=1.00~1.03,P=0.022;ox-LDL:OR=1.06,95%CI=1.01~1.12,P=0.023)。结论 CAD患者血清C1q水平升高;且ACS患者C1q水平高于SCAD患者。ACS患者血清C1q与ox-LDL水平显著独立相关。血清C1q水平可望作为预测与区分ACS和SCAD的新指标。     

部分血浆凝血因子活性测定在急性冠脉综合征中的应用价值

目的观察急性冠脉综合征（ACS）患者部分凝血因子活性水平,探讨其在ACS发病中的意义。方法测定100例急性心肌梗死（AMI）和69例不稳定性心绞痛（UAP）患者急性期凝血因子Ⅴ、Ⅶ、Ⅷ、Ⅹ、Ⅺ活性（FⅤ：C、FⅦ：C、FⅧ：C、FⅩ：C、FⅪ：C）,并与120例稳定性心绞痛（SAP）患者和80例健康对照组进行比较,分析这些因子活性水平与AMI和UAP急性期的关系。结果AMI和UAP患者急性期FⅤ：C、FⅦ：C、FⅧ：C、FⅩ：C、FⅪ：C水平明显高于SAP组和健康对照组（P〈0．05））;SAP组和健康对照组比较差异无统计学意义（P〉0．05）。结论ACS患者急性期FⅤ：C、FⅦ：C、FⅧ：C、FⅩ：C、FⅪ：C水平明显升高,存在高凝状态。     

Thrombin generation in patients with a first acute myocardial infarction

Summary. Background: Despite improved treatment options, myocardial infarction is still an important cause of morbidity and mortality. One of the contributing mechanisms in the acute myocardial infarction (AMI) is plasma hypercoagulability. Methods: We investigated hypercoagulability in 135 (first) patients with AMI using thrombin generation (TG) testing. TG testing was performed in plasmas, drawn upon admission and before medication administration, and subsequently after 4 days, 3 and 6 months. Further, we evaluated determinants of thrombin generation using multiple regression analysis of major coagulation proteins and inhibitors. Admission TG results were also related to 1‐year outcome: cardiovascular death, recurrent myocardial infarction, a second coronary intervention [percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] and ischemic stroke. Results: At day 0, the TG parameters peak height, endogenous thrombin potential (ETP) and lag time were increased compared with a reference population. Peak height and lag time stayed persistently increased in patients. The lowest half of the ETP values was statistically not significantly associated with an occurrence of endpoints. The lowest half of the ETP values combined with the upper half of the D‐dimer values were associated with endpoints; odds ratio 5.8 (1.1–30.7). Tissue factor pathway inhibitor (TFPI) seems to be an important determinant of TG in AMI and healthy persons. Conclusions: TG reflects acute hypercoagulability during AMI and partly also in the 6‐month period after the acute event. TG shows a trend of an inverse association with risk of recurrent ischemic cardiovascular complications. Unraveling mechanisms in TG might improve our understanding of the pathophysiology of AMI and direct future improvements in medical care.     

血浆D-二聚体检测在急性冠脉综合征中的临床价值

摘要：目的：探讨急性冠脉综合征（ACS）患者血浆D-二聚体（D-D）水平及其临床应用价值。 方法：检测并比较75例体检健康者及149例不稳定型心绞痛（UAP）、101例非ST段抬高型心肌梗死（NSTEMI）、107例ST段抬高型心肌梗死（STEMI）患者血浆D-D水平,用ROC曲线评价D-D的诊断性能。 结果：健康人对照组及UAP组、NSTEMI组、STEMI组患者血浆D-D水平分别为329(126,537)、634(200,1 333)、771(299,1 400)和1 160(388,2 418) μg/L;1支、2支和≥3支血管病变组患者血浆D-D水平分别为817(200,1 751)、1 002(262,2 418)和1 276(322,2 341) μg/L。STEMI组患者血浆D-D水平高于UAP组和NSTEMI组（U分别为198.1、96.5,P均<0.01）;≥3支血管病变组高于单支血管病变组（U=459.9,P<0.01）。D-D诊断STEMI的ROC曲线下面积为0.866（95%CI：0.793~0.939）,当cut off值为793 μg/L时,D-D诊断STEMI的敏感性为84.8%,特异性为69.3%。经Cox比例风险模型多因素分析,血浆D-D水平增高是ACS患者死亡风险的独立预测指标。 结论：ACS患者血浆D-D水平显著增高,特别是在辅助诊断STEMI时有较高的敏感性,且具有预后判断的参考价值。     

冠状动脉多支病变对急诊经皮冠状动脉介入治疗患者住院期间预后的影响

目的 了解冠状动脉多支病变对急诊经皮冠状动脉介入治疗患者的临床特点及对住院期间预后的影响。方法 连续入选接受急诊经皮冠状动脉介入治疗的急性冠状动脉综合征患者。根据冠状动脉造影结果,分为单支病变组35例,多支病变组37例,分析两组临床特点及住院期间心脏不良事件（MACE）的发生情况。结果 多支病变组年龄,高血压病,糖尿病,吸烟,入院时血糖,甘油三酯明显高于单支病变组（P<0.05）。且多支病变组术前左心室射血分数低于单支病变组（P=0.001）。与单支病变组比较,多支病变组MACE发生率明显升高（P<0.05）。单因素分析得出,多支病变、糖尿病、入院时血糖、肌酐为MACE事件的危险因素,通过Logistic回归分析,入院时血糖为MACE事件的独立危险因子（OR=1.526,P=0.009）。结论 急诊经皮冠状动脉介入治疗患者合并冠状动脉多支病变时,具有多重危险因素,心脏主要不良事件发生率高。     

C-reactive protein contributes to the hypercoagulable state in coronary artery disease

OBJECTIVES: Elevated plasma C-reactive protein (CRP) levels predict coronary events, but it is unclear whether CRP plays a role in thrombosis associated with these events. We investigated tissue factor (TF) induction by CRP on peripheral blood mononuclear cells (PBMC) from patients with coronary disease. PATIENTS AND METHODS: PBMC from 35 patients with stable angina (SA) in study 1, 10 male patients with SA, 10 with unstable angina (UA) and 10 matched controls in study 2, and 25 patients with inflammatory disorders (ID) and 24 normal controls in study 3 were stimulated with CRP, interferon-gamma (IFN) or lipopolysaccharide (LPS), or their combination. PBMC from additional normal donors were also stimulated with CRP in adherent and non-adherent conditions, and TF activity, antigen and mRNA expression detected. RESULTS: CRP (5-25 microg mL(-1)) dose dependently induced more TF on PBMC from SA patients than 42 contemporary controls (P = 0.001, study 1). Compared with controls, patients with SA or UA had higher basal, and much higher CRP- or CRP/LPS-induced monocyte TF activity although serum CRP levels were similar (study 2). IFN induced monocyte TF activity in patients with angina, but not in controls. Basal or CRP-induced TF levels did not differ between controls and ID, even though ID patients had much higher serum CRP levels (study 3). CRP-induced monocyte TF activity correlated with serum CRP levels in controls (P = 0.005) and ID (P = 0.007) in study 3, but not in patients with angina (P =0.84) in study 2. CRP induced more TF activity, protein and mRNA under adherent than non-adherent conditions implying that it may mainly target macrophages in lymphocyte-rich lesions. CONCLUSIONS: Our results indicate that monocytes from patients with angina are preactivated and express TF but CRP is unlikely to be a major priming factor in vivo. IFN and CRP further increase TF levels that may contribute to the hypercoagulable state in coronary disease.